Protective effect of rasagiline in aminoglycoside ototoxicity.

Sensorineural hearing losses (SNHLs; e.g., ototoxicant- and noise-induced hearing loss or presbycusis) are among the most frequent sensory deficits, but they lack effective drug therapies. The majority of recent therapeutic approaches focused on the trials of antioxidants and reactive oxygen species (ROS) scavengers in SNHLs. The rationale for these studies was the prominent role of disturbed redox homeostasis and the consequent ROS elevation. Although the antioxidant therapies in several animal studies seemed to be promising, clinical trials have failed to fulfill expectations. We investigated the potential of rasagiline, an FDA-approved monomanine oxidase type B inhibitor (MAO-B) inhibitor type anti-parkinsonian drug, as an otoprotectant. We showed a dose-dependent alleviation of the kanamycin-induced threshold shifts measured by auditory brainstem response (ABR) in an ototoxicant aminoglycoside antibiotic-based hearing loss model in mice. This effect proved to be statistically significant at a 6-mg/kg (s.c.) dose. The most prominent effect appeared at 16kHz, which is the hearing sensitivity optimum for mice. The neuroprotective, antiapoptotic and antioxidant effects of rasagiline in animal models, all targeting a specific mechanism of aminoglycoside injury, may explain this otoprotection. The dopaminergic neurotransmission enhancer effect of rasagiline might also contribute to the protection. Dopamine (DA), released from lateral olivocochlear (LOC) fibers, was shown to exert a protective action against excitotoxicity, a pathological factor in the aminoglycoside-induced SNHL. We have shown that rasagiline enhanced the electric stimulation-evoked release of DA from an acute mouse cochlea preparation in a dose-dependent manner. Using inhibitors of voltage-gated Na+-, Ca2+ channels and DA transporters, we revealed that rasagiline potentiated the action potential-evoked release of DA by inhibiting the reuptake. The complex, multifactorial pathomechanism of SNHLs most likely requires drugs acting on multiple targets for effective therapy. Rasagiline, with its multi-target action and favorable adverse effects profile, might be a good candidate for a clinical trial testing the otoprotective indication

Persistence of dissolved organic matter explained by molecular changes during its passage through soil

Dissolved organic matter affects fundamental biogeochemical processes in the soil such as nutrient cycling and organic matter storage. The current paradigm is that processing of dissolved organic matter converges to recalcitrant molecules (those that resist degradation) of low molecular mass and high molecular diversity through biotic and abiotic processes. Here we demonstrate that the molecular composition and properties of dissolved organic matter continuously change during soil passage and propose that this reflects a continual shifting of its sources. Using ultrahigh-resolution mass spectrometry and nuclear magnetic resonance spectroscopy, we studied the molecular changes of dissolved organic matter from the soil surface to 60 cm depth in 20 temperate grassland communities in soil type Eutric Fluvisol. Applying a semi-quantitative approach, we observed that plant-derived molecules were first broken down into molecules containing a large proportion of low-molecular-mass compounds. These low-molecular-mass compounds became less abundant during soil passage, whereas larger molecules, depleted in plant-related ligno-cellulosic structures, became more abundant. These findings indicate that the small plant-derived molecules were preferentially consumed by microorganisms and transformed into larger microbial-derived molecules. This suggests that dissolved organic matter is not intrinsically recalcitrant but instead persists in soil as a result of simultaneous consumption, transformation and formation

Pharmacological Analysis of Ionotropic Glutamate Receptor Function in Neuronal Circuits of the Zebrafish Olfactory Bulb

Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb

Evaluation of a novel magneto-optical method for the detection of malaria parasites

Improving the efficiency of malaria diagnosis is one of the main goals of current malaria research. We have recently developed a magneto-optical (MO) method which allows high-sensitivity detection of malaria pigment (hemozoin crystals) in blood via the magnetically induced rotational motion of the hemozoin crystals. Here, we evaluate this MO technique for the detection of Plasmodium falciparum in infected erythrocytes using in-vitro parasite cultures covering the entire intraerythrocytic life cycle. Our novel method detected parasite densities as low as approximately 40 parasites per microliter of blood (0.0008% parasitemia) at the ring stage and less than 10 parasites/microL (0.0002% parasitemia) in the case of the later stages. These limits of detection, corresponding to approximately 20 pg/microL of hemozoin produced by the parasites, exceed that of rapid diagnostic tests and compete with the threshold achievable by light microscopic observation of blood smears. The MO diagnosis requires no special training of the operator or specific reagents for parasite detection, except for an inexpensive lysis solution to release intracellular hemozoin. The devices can be designed to a portable format for clinical and in-field tests. Besides testing its diagnostic performance, we also applied the MO technique to investigate the change in hemozoin concentration during parasite maturation. Our preliminary data indicate that this method may offer an efficient tool to determine the amount of hemozoin produced by the different parasite stages in synchronized cultures. Hence, it could eventually be used for testing the susceptibility of parasites to antimalarial drugs

Microbial diversity in waters, sediments and microbial mats evaluated using fatty acid-based methods

The review summarises recent advances towards a greater comprehensive assessment of microbial diversity in aquatic environments using the fatty acid methyl esters and phospholipid fatty acids approaches. These methods are commonly used in microbial ecology because they do not require the culturing of micro-organisms, are quantitative and reproducible and provide valuable information regarding the structure of entire microbial communities. Because some fatty acids are associated with taxonomic and functional groups of micro-organisms, they allow particular groups of micro-organisms to be distinguished. The integration of fatty acid-based methods with stable isotopes, RNA and DNA analyses enhances our knowledge of the role of micro-organisms in global nutrient cycles, functional activity and phylogenetic lineages within microbial communities. Additionally, the analysis of fatty acid profiles enables the shifts in the microbial diversity in pristine and contaminated environments to be monitored. The main objective of this review is to present the use of lipid-based approaches for the characterisation of microbial communities in water columns, sediments and biomats